This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vucetic, Z.
Right arrow Articles by Soprano, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vucetic, Z.
Right arrow Articles by Soprano, D. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2008, p. 2549-2558, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01199-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Acinus-S' Represses Retinoic Acid Receptor (RAR)-Regulated Gene Expression through Interaction with the B Domains of RARs{triangledown} ,{dagger}

Zivjena Vucetic,1 Zhenping Zhang,1 Jianhua Zhao,2 Fang Wang,1 Kenneth J. Soprano,2,3 and Dianne Robert Soprano1,3*

Department of Biochemistry,1 Department of Microbiology and Immunology,2 Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 191403

Received 5 July 2007/ Returned for modification 4 September 2007/ Accepted 20 January 2008

The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). Modulation of transcription by RARs/RXRs is achieved through two activation functions, ligand-independent AF-1 and ligand-dependent AF-2, located in the A/B and E domains, respectively. While the coregulatory proteins that interact with the E domain are well studied, the A/B domain-interacting partners and their influence(s) on the function of RARs are poorly understood. Acinus-S' is an ubiquitous nuclear protein that has been implicated in inducing apoptotic chromatin condensation and regulating mRNA processing. Our data demonstrate that Acinus-S' can specifically repress ligand-independent and ligand-dependent expression of a DR5 RA response element(RARE)-dependent reporter gene and several endogenous RAR-regulated genes in a dose-dependent and gene-specific manner. Chromatin immunoprecipitation assays show that Acinus-S' associates with RAREs within the promoters of endogenous genes independent of RA treatment. Furthermore, the C-terminal end of Acinus-S' and the B domain of RARβ interact independently of ligand, and the C-terminal end of Acinus-S' is sufficient for the repression of RAR-regulated gene expression. Finally, histone deacetylase activity only partially accounts for the repressive effect of Acinus-S' on RAR-dependent gene expression. These findings identify Acinus-S' as a novel RAR-interacting protein that regulates the expression of a subset of RAR-regulated genes through direct binding to the N-terminal B domains of RARs.

* Corresponding author. Mailing address: Department of Biochemistry, Temple University School of Medicine, 3440 N. Broad Street, Philadelphia, PA 19140. Phone: (215) 707-3266. Fax: (215) 707-7536. E-mail: dsoprano{at}temple.edu

{triangledown} Published ahead of print on 4 February 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, April 2008, p. 2549-2558, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01199-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»